Two types of eating disorders, bulimia nervosa in normal weight women (NWB) and restricting-type anorexia nervosa (RAN), may provide insights into permissive or protective factors contributing to psychoactive substance use disorders (PSUD) in humans. These two eating disorders, while of the grouped together are at opposite extremes for rate of PSUD (common in NWB, rare in RAN) pathologic feeding behavior (binging vs restrictive eating) and impulse control (poor in NWB high in RAN). Studies in humans at risk for PSUD have identified factors which may play a contributory role to PSUD such as behavioral under control, emotionality, personality, or sensitization to the reinforcing effects of drugs. Our preliminary data support the possibility that a high rate of PSUD in NWB may be related to the presence of such risk factors. We will explore whether the opposite of these risk factors protects RAN from PSUD. It is not certain how to most effectively measure such risk factors in women with eating disorders. In this R21 application, which is exploratory in nature. Aim 1 will determine which instruments best discriminate risk factors such as impulse dyscontrol, negative unstable mood states or personality. We will study five groups of women over two years; 20 NWB with PSUD, 20 NWB without a lifetime diagnosis of PSUD 20 women with RAN and two groups of control women (without an eating disorder); 20 control women with PSUD and 20 women without PSUD. We will explore whether risk factors occur in all NWB women or whether RAN women have opposite risk factors for PSUD. We hypothesize that disturbances of impulse control and mood stability are a reflection of a more pervasive psychobiologic disturbance of reactivity. In Aim 2, we seek to replicate and extend our preliminary data which suggest that NWB women may have reduced salivary habituation in response to food intake. In contrast, we hypothesize that RAN women will rapidly habituate and thus may be insensitive to the reinforcing effects of food or drugs. We will also determine whether such responses (in terms of heart rate and skin conductance) generalize to nonfood related stimuli such as auditory tone. Our long-term goal is to understand how neurotransmitters such as serotonin, may play a permissive/protective role in the development of PSUD in patients with eating disorders. However, a major impediment to such work is having an accurate and reliable means of assessing in women with eating disorders, the behavioral expression of risk factor that may be related to disturbances of neurotransmitter activity. Thus a major focus of this R21 exploratory application is to develop a laboratory behavior task which reflects behavioral under control in NWB women. If successful, future studies will test whether serotonin-specific pharmacologic agents of drugs affect behavioral under control in women with eating disorders. This R21 application (which was response to program announcement PA-93-060) is a resubmission of 1R21DA/MH09369-01.